Metastasis, the spread of cancer from a primary site to distant organs, still remains the main cause of death for most cancer patients. Despite years of research, the genetic mechanisms involved in the process are ill defined. Such information is of special importance in cancer prognosis given the uncertain course of the disease. The greatest obstacle to the successful treatment of the cancer patient continues to be the lack of sound prognostic markers, indeed cancer prognosis can not always be accurately assessed using current tumor grading techniques.
The mechanisms which regulate the growth of the cancer cell are of particular relevance to the development of strategies for the treatment of metastatic cancer. Individual patients exhibit extreme variation in cancer progression. In some patients the cancer remains localized, whereas in other the cancer metastasizes quickly. Stromal-epithelial interactions (mediated through cytokine and other growth factors) with the extracellular matrix play a role in development of metastatic cancer.
Using the technique of differential display polymerase chain reaction, it has been found that the cytokine, macrophage migration inhibitory factor (MIF), is one gene whose expression is altered in metastatic prostate cancer when compared to normal tissue (Meyer-Siegler, K. Hudon PB). Enhanced expression of macrophage migration inhibitory factor in prostatic adenocarcinoma metastases. Urology 48: 448-452, 1996.
MIF was first described thirty years ago and was designated as a cytokine, a chemical mediator which regulates cell growth by inducing the expression of specific target genes. The initial described function of MIF was as a regulator of inflammation and immunity. However, current research suggests an even greater role for MIF. It is expressed in the brain, and eye lens, is a delayed early response gene in fibroblasts, and it has been reported that this protein can be found in prostate tissues. MIF has been shown to be a pituitary, as well as macrophage cytokine and a critical mediator of septic shock. Recent studies also suggest that MIF may have an autocrine function for embryo development and is produced by the Leydig cells of the testes. Thus, it appears that this cytokine may play a fundamental role in cell growth regulation and possibly development.